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BACKGROUND: Lipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain. METHODS: Using the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums. RESULTS: Using LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10- 5) and slower walking pace (OR = 0.918, P = 6.06 × 10- 9). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10- 3), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10- 3) and decelerate walking pace (OR = 0.932, P = 1.43 × 10- 6), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10- 6). Meta-analysis further supported the robustness of these causal associations. CONCLUSIONS: Genetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.
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Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Pró-Proteína Convertase 9 , Sarcopenia , Humanos , Sarcopenia/genética , Pró-Proteína Convertase 9/genética , Hidroximetilglutaril-CoA Redutases/genética , LDL-Colesterol/sangue , LDL-Colesterol/genética , Proteínas de Membrana Transportadoras/genética , Hipolipemiantes/uso terapêutico , Hipolipemiantes/efeitos adversos , Proteínas de Membrana/genética , Masculino , Feminino , Idoso , Força da MãoRESUMO
PURPOSE: The prognosis of recurrent glioblastoma (rGBM) is poor, and there is currently no effective treatment strategy. Sonodynamic therapy (SDT) is a new method for cancer treatment that uses a combination of low-frequency ultrasound and sonosensitisers to produce antitumor effects, which have shown good therapeutic effects in preclinical studies. Therefore, we initiated an open, prospective pilot study to evaluate the safety, tolerability, and efficacy of SDT for the treatment of rGBM. METHODS: Nine patients with rGBM were enrolled who had received multiple treatments, but the nidus continued to progress without additional standard treatments. After MRI localisation, porphyrin drugs were injected, and intermittent low-frequency ultrasound therapy was performed for five days. RESULTS: None of the nine patients in this clinical trial showed any clinical, neurological, haematological, or skin-targeted adverse effects associated with SDT. After the completion of the trial, one patient maintained stable disease, and eight patients experienced disease progression. Among the eight with progressive disease, the median progression-free survival time was 84 days. Four patients died, and the median overall survival duration after recurrence was 202.5 days. CONCLUSION: The number of patients in this study was small; therefore, a long-term survival benefit was not demonstrated. However, this study suggests that SDT has potential as a treatment for rGBM and warrants further exploration. Trial information: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ): ChiCTR2200065992. November 2, 2022, retrospectively registered.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Estudos Prospectivos , Projetos Piloto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologiaRESUMO
Graphene oxide (GO) is an ideal hydrogel material because of its water solubility, non-toxicity, and excellent mechanical properties. Here, we added GO to oligo(lysine)-modified F127 to prepare a series of FLGO composite hydrogels. The FLGO hydrogel was thermally induced, stable and injectable. And the content of GO would affect the sol-gel transition, rheological properties and glass transition temperature of the FLGO hydrogel. GO was connected to the matrix through electrostatic interactions and hydrogen bonds. The cross-linking effect of GO enhanced the FLGO hydrogel. We also studied the release properties of the FLGO hydrogel loaded with anticancer drug 5-fluorouracil. Compared with F127 hydrogel, the FLGO hydrogel showed a linear, slower and stable release pattern within one week. The release rate of FLGO hydrogel could be adjusted by the pH and it was faster under acidic conditions. Therefore, the FLGO hydrogel is expected to be used as a drug release system in the field of biomedicine.
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Grafite , Hidrogéis , Preparações de Ação Retardada , Liberação Controlada de FármacosRESUMO
As key equipment in modern industry, it is important to diagnose and predict the health status of bearings. Data-driven methods for remaining useful life (RUL) prognostics have achieved excellent performance in recent years compared to traditional methods based on physical models. In this paper, we propose a novel data-driven method for predicting the remaining useful life of bearings based on a deep graph convolutional neural network with spatiotemporal domain convolution. This network uses the average sliding root mean square (ASRMS) as the health factor to identify the healthy and degraded states, and then uses correlation coefficient analysis on the hybrid features of the degraded data to construct a spatial graph according to the strength of the correlation between the obtained features. In the time domain, we introduce historical data as the input to the temporal convolution. After the data are processed by the spatial map and the temporal dimension, we perform the prediction of the remaining useful life. The experimental results show the accuracy of the method.
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Modelos Teóricos , Redes Neurais de Computação , PrognósticoRESUMO
Phase-drift elimination is crucial to vibration recovery in the coherent detection phase-sensitive optical time domain reflectometry system. The phase drift drives the whole phase signal fluctuation as a baseline, and its negative effect is obvious when the detection time is long. In this paper, empirical mode decomposition (EMD) is presented to extract and eliminate the phase drift adaptively. It decomposes the signal by utilizing the characteristic time scale of the data, and the baseline is eventually obtained. It is validated by theory and experiment that the phase drift deteriorates seriously when the length of the vibration region increases. In an experiment, the phase drift was eliminated under the conditions of different vibration frequencies of 1 Hz, 5 Hz, and 10 Hz. The phase drift was also eliminated with different vibration intensities. Furthermore, the linear relationship between phase and vibration intensity is demonstrated with a correlation coefficient of 99.99%. The vibrations at 0.5 Hz and 0.3 Hz were detected with signal-to-noise ratios (SNRs) of 55.58 dB and 64.44 dB. With this method, when the vibration frequency is at the level of Hz or sub-Hz, the phase drift can be eliminated. This contributes to the detection and recovery of low-frequency perturbation events in practical applications.
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Though evaluation and analysis on the relevant literatures at home and abroad in recent years, the total number of retrieved literature was 2 664. According to the inclusion criteria and exclusion criteria,the literatures were screened out, and the results were as followsï¼374 literatures. To analyse the advantages and evidence of Chinese medicine in the prevention and treatment of adult acute tonsillitis. It is found to be effective, convenient and practical for the treatment of acute tonsillitis by traditional Chinese medicine (TCM) like treatment according to syndrome differentiation, Chinese patent drug, self Chinese medicine prescription and external treatment. TCM has obvious advantages in the prevention and treatment of acute tonsillitis, has the function of supplementing or substituting antibiotics, and has the function of regulating the defense function of organism.
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Medicina Tradicional Chinesa , Tonsilite/prevenção & controle , Tonsilite/terapia , Adulto , Medicamentos de Ervas Chinesas/uso terapêutico , HumanosRESUMO
ß-Carotene and astaxanthin are two carotenoids with powerful antioxidant properties, but the binding mechanisms of ß-carotene/astaxanthin to proteases remain unclear. In this study, the interaction of these two carotenoids with trypsin and pepsin was investigated using steady-state and time-resolved fluorescence measurements, synchronous fluorescence spectroscopy, UV-vis absorption spectroscopy and circular dichroism (CD) spectroscopy. The experimental results indicated that the quenching mechanisms of trypsin/pepsin by the two carotenoids are static processes. The binding constants of trypsin and pepsin with these two carotenoids are in the following order: astaxanthin-trypsin > astaxanthin-pepsin > ß-carotene-trypsin > ß-carotene-pepsin, respectively. Thermodynamic investigations revealed that the interaction between the two carotenoids and trypsin/pepsin is synergistically driven by enthalpy and entropy, and hydrophobic forces and electrostatic attraction have a significant role in the reactions. In addition, as shown by synchronous fluorescence spectroscopy, UV-vis absorption spectroscopy and CD, the two carotenoids may induce conformational and microenvironmental changes in trypsin/pepsin. The study provides an accurate and full basic data for clarifying the binding mechanisms of the two carotenoids with trypsin/pepsin and is helpful in understanding their effect on protein function and their biological activity in vivo.
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Pepsina A/química , Tripsina/química , beta Caroteno/química , Dicroísmo Circular , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica , Xantofilas/químicaRESUMO
Mucormycosis is an invasive opportunistic fungal infection, which may be lethal and mostly affects patients with immunodeficiency or diabetes mellitus. Among Mucorales fungi, Rhizopus spp. is the most common cause of mucormycosis, followed by genera such as Mucor and Lichtheimia. Here we report a patient with severe COVID-19 infection who developed nasal pain, facial swelling, prominent black eschar on the nasal root. CT scan revealed pansinusitis along the maxillary, ethmoidal, and sphenoid sinuses. Mixed mold infection with Rhizopus microsporus and Mucor racemosus was detected by blood metagenomics next-generation sequencing (mNGS) and later nasal mucosa histological investigation confirmed mucormycosis. Severe COVID-19 infection led to the patient's thrombocytopenia and leukopenia. Later disseminated mucormycosis aggravated the infection and sepsis eventually resulted in death. It is the first case report of mucormycosis in which R. microsporus and M. racemosus as the etiologic agents were found simultaneously in one patient. COVID-19 infection combined with disseminated mucormycosisis can be fatal and mNGS is a fast, sensitive and accurate diagnostic method for fungi detection.
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BACKGROUND: Despite numerous investigations into the relationship between physical activities (PA) and epilepsy, the causal effects remain contentious. Thus, we conducted a two-sample Mendelian randomization (MR) study to assess the potential causality. METHODS: Single-nucleotide polymorphisms (SNPs) predisposed to self-reported moderate and vigorous physical activities (MPA and VPA) and overall acceleration average (OAA) calculated through wrist-worn accelerometers were selected as exposure instrumental variables. Five subtypes of epilepsy, including all epilepsy, focal epilepsy and generalized epilepsy (with or without each other), focal epilepsy-strict definition and generalized epilepsy-strict definition (without overlap), were chosen as the outcomes. The MR study utilized the inverse-variance weighted (IVW) method as the primary analytical tool, supplemented by MR-Egger, simple mode, weighted mode, and weighted median methods. Cochran's Q and MR-Egger intercept tests were employed to assess heterogeneity and pleiotropy, while MR pleiotropy residual sum and outlier and leave-one-out analyses were conducted to identify potential SNP outliers. RESULTS: The study indicated that OAA was genetically linked to a decreased risk of both focal epilepsy (OR = 0.812, 95% CI: 0.687-0.960, p = .015, IVW) and focal epilepsy-strict definition (OR = 0.732, 95% CI: 0.596-0.900, p = .003, IVW; OR = 0.749, 95% CI: 0.573-0.979, p = .035, Weighted median). Genetically predicted MPA and VPA did not exhibit a causal association with all epilepsy or its subtypes (p>.05). No evidence of heterogeneity, pleiotropy, or SNP outlier was observed. CONCLUSIONS: Our findings suggested that PA with accelerometer monitoring may potentially reduce the risk of focal epilepsy, while there is no evidence supporting causal association between self-reported MPA or VPA and either focal or generalized epilepsy.
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Epilepsias Parciais , Epilepsia Generalizada , Epilepsia , Humanos , Análise da Randomização Mendeliana , Epilepsia/genética , Exercício FísicoRESUMO
STUDY OBJECTIVES: Narcolepsy type 1 (NT1), characterized by cataplexy and orexin deficiency, is a rare and frequently debilitating neurological disorder. It has been noted to have connections with the gut microbiota, yet the exact causal relationships remain unclear. METHODS: We conducted a comprehensive bidirectional Mendelian randomization (MR) study to rigorously investigate the causal links between the gut microbiota and NT1, utilizing genetic datasets from the MiBioGen consortium and FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was employed to obtain the primary MR estimates, supplemented by several alternative methods as well as sensitivity analyses including Cochran's Q, MR-Egger, MR pleiotropy residual sum and outlier, leave-one-out, and genetic colocalization. RESULTS: Our findings indicated that an increased relative abundance of five genera including Blautia (pâ =â 4.47E-5), Collinsella (pâ =â 0.036), Gordonibacter (pâ =â 0.047), Hungatella (pâ =â 0.015), and Lachnospiraceae UCG010 (pâ =â 0.027) may be associated with a decreased risk of NT1. Conversely, an increased relative abundance of class Betaproteobacteria (pâ =â 0.032), genus Alloprevotella (pâ =â 0.009), and genus Ruminiclostridium6 (pâ =â 0.029) may potentially heighten the risk of NT1. The onset of NT1 may lead to a decrease in the relative abundance of genus Eubacterium eligens group (pâ =â 0.022), while a increase in the family Family XI (pâ =â 0.009), genus Hungatella (pâ =â 0.005), genus Prevotella (pâ =â 0.013), and unknown genus id.2001 (pâ =â 0.019). These findings remained robust under all sensitivity analyses. CONCLUSIONS: Our results offer robust evidence for the bidirectional causal links between particular gut microbial taxa and NT1, underscoring the significance of the microbiota-gut-brain axis in the pathological process of NT1.
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Cataplexia , Microbioma Gastrointestinal , Narcolepsia , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Narcolepsia/genética , Estudo de Associação Genômica AmplaRESUMO
BACKGROUND: Migraine is a common and burdensome neurological disorder. The causal relationship between sedentary behaviours (SBs) and migraine remains instinct. We aimed to evaluate the roles of SBs including watching TV, using computer and driving in the risk of migraine. METHODS: We conducted a univariable and multivariable Mendelian randomization (MR) study based on summary datasets of large genome-wide association studies. The inverse variance weighted method was utilized as the primary analytical tool. Cochran's Q, MR-Egger intercept test, MR pleiotropy residual sum and outlier and leave-one-out were conducted as sensitivity analysis. Additionally, we performed a meta-analysis to combine the causal estimates. RESULTS: In the discovery analysis, we identified causal associations between time spent watching TV and an increased risk of migraine (p = 0.015) and migraine without aura (MO) (p = 0.002). Such causalities with increasing risk of migraine (p = 0.005), and MO (p = 0.006) were further verified using summary datasets from another study in the replication analysis. There was no significant causal association found between time spent using computer, driving and migraine or its two subtypes. The meta-analysis and multivariable MR analysis also strongly supported the causal relationships between time spent watching TV and an increased risk of migraine (p = 0.0003 and p = 0.034), as well as MO (p < 0.0001 and p = 0.0004), respectively. These findings were robust under all sensitivity analysis. CONCLUSIONS: Our study suggested that time spent watching TV may be causally associated with an increased risk of migraine, particularly MO. Large-scale and well-designed cohort studies may be warranted for further validation. SIGNIFICANCE STATEMENT: This study represents the first attempt to investigate whether a causal relationship exists between SBs and migraine. Utilizing MR analysis helps mitigate reverse causation bias and confounding factors commonly encountered in observational cohorts, thereby enhancing the robustness of derived causal associations. Our MR analysis revealed that time spent watching TV may serve as a potential risk factor for migraine, particularly MO.
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Objective: To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated. Methods: A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model. Results: The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model. Conclusion: PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.
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OBJECTIVE: To analyze the efficacy and adverse effects of anti-PD-1 immune checkpoint inhibitors aimed at nasopharyngeal carcinoma (NPC). METHODS: During the first stage of the study, using 40 patients with stage III/IVa NPC treated with anti-PD-1 immune checkpoint inhibitors in combination with chemoradiotherapy as a first-line treatment (observation group) and 70 patients with NPC treated with chemoradiotherapy alone (control group). In the second stage of the study, 88 patients with NPC treated with immune checkpoint inhibitors were grouped according to the number of lines of immunotherapy, the number of times, and the types of application. RESULTS: Observation of the short-term effects in the first stage indicated that the objective response rate (ORR) of the observation group and the control group against primary foci of NPC was 75.0% versus 40.0%; the mortality rate of the observation group was much lower than that of the control group. The overall first-line treatment evaluation of the observation vs. control groups were as follows: ORR (67.5% vs. 38.6%); median PFS (17.52 vs. 17.21 months); and median OS (18.68 vs. 18.14 months), respectively (p < 0.05). The second stage of the study had an ORR of 53.4%, and the efficacy of immunotherapy was related to staging, timing, and frequency. CONCLUSION: Anti-PD-1 immune checkpoint inhibitors combined with chemoradiotherapy as the first-line treatment for nasopharyngeal carcinoma may improve patient outcomes significantly. Timing, frequency, and the type of immunotherapy exerted an effect on the efficacy of immunotherapy. Adverse effects that occurred during treatment were tolerable and controllable.
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Quimiorradioterapia , Inibidores de Checkpoint Imunológico , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Receptor de Morte Celular Programada 1 , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estadiamento de Neoplasias , Resultado do Tratamento , Adulto JovemRESUMO
Emerging memories have been developed as new physical infrastructures for hosting neural networks owing to their low-power analog computing characteristics. However, accurately and efficiently programming devices in an analog-valued array is still largely limited by the intrinsic physical non-idealities of the devices, thus hampering their applications in in-situ training of neural networks. Here, we demonstrate a passive electrochemical memory (ECRAM) array with many important characteristics necessary for accurate analog programming. Different image patterns can be open-loop and serially programmed into our ECRAM array, achieving high programming accuracies without any feedback adjustments. The excellent open-loop analog programmability has led us to in-situ train a bilayer neural network and reached software-like classification accuracy of 99.4% to detect poisonous mushrooms. The training capability is further studied in simulation for large-scale neural networks such as VGG-8. Our results present a new solution for implementing learning functions in an artificial intelligence hardware using emerging memories.
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Recently, the dysregulation of circRNAs has been increasingly implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). Among these circRNAs, circMAN1A2 has been highlighted for the up-regulated expression in NPC, whereas the underlying mechanisms have not been clearly established. Thus, the aim of this study was to delineate the tumor-supporting role of circMAN1A2 in the oncogenesis and metastases of NPC. We validated through qRT-PCR that circMAN1A2 was highly expressed in NPC tissues and NPC cells. Survival analysis through Kaplan-Meier method showed that the overall survival, disease-free survival, and distant metastasis-free survival of patients was negatively correlated with the expression of circMAN1A2. Then, gain- and loss-of function assays demonstrated that circMAN1A2 knockdown could impede the proliferation, migration, invasion, and EMT in NPC cells. Further, we conducted dual luciferase reporter gene, RIP, and RNA pull down assays, unveiling that circMAN1A2 functioned as a sponge of miR-135a-3p, and miR-135a-3p targeted UBR5. Additionally, UBR5 interacted with ATMIN to foster the ubiquitination of ATMIN, thereby expediting the malignant behaviors of NPC cells as well as the lung and inguinal lymph node metastases of NPC tumors in vivo. Together, our study uncovered the tumor-initiating and pro-metastatic role of circMAN1A2-miR-135a-3p-UBR5-ATMIN axis in NPC regulation that may be a potential therapeutic target for human NPC.
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MicroRNAs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , RNA Circular , Ubiquitina-Proteína Ligases , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Circular/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
Background: Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut microbiome, gut microbiome-derived metabolites, and MG using Mendelian randomization (MR) approach. Methods: Summary-level genetic datasets from large-scale genome-wide association studies regarding 196 gut microbial taxa from the MiBioGen consortium (n=18,340), 72 derived metabolites from the TwinsUK and KORA studies (n=7,824), and antiacetylcholine receptor (AChR) antibody-positive MG (case=1,873, control=36,370) were employed for MR causal estimates. The inverse-variance weighted (IVW) method was utilized as the main analysis with MR-Egger, maximum likelihood, simple mode, and weighted median as complements. The tests of Cochran's Q, MR-Egger intercept, Steiger, MR-PRESSO and leave-one-out were implemented for sensitivity analyses. Results: The forward MR estimates of IVW revealed significant causal associations of the abundance of phylum Actinobacteria, class Gammaproteobacteria, family Defluviitaleac, family Family XIII, and family Peptococcaceae with a reduced risk of MG. Conversely, the abundance of phylum Lentisphaerae, order Mollicutes RF9, order Victivallales, and genus Faecalibacterium was causally associated with an increased risk of MG. The reversed MR analysis proved negative causal correlations between the MG and the abundance of family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum. Regarding the derived metabolites, the IVW estimates revealed that elevated levels of beta-hydroxyisovalerate and methionine were causally associated with a decreased risk of MG, while increased levels of choline and kynurenine were linked to an increased risk of MG. Furthermore, genetically predicted MG was associated with a decreased level of cholesterol. The results obtained from complementary MR methods were similar. These findings remained robust in all sensitivity analyses. Conclusion: Our MR findings support the causal effects of specific gut microbiome taxa and derived metabolites on AChR antibody-positive MG, and vice versa, yielding novel insights into prevention and therapy targets of MG. Future studies may be warranted for validation and pursuing the precise mechanisms.
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Microbioma Gastrointestinal , Miastenia Gravis , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Miastenia Gravis/genética , AutoanticorposRESUMO
Objective:To observe and analyze the changes in subjective visual verticalï¼SVVï¼ after otolith reduction in patients with BPPV. Methods:46 patients with confirmed BPPV recieving successful otolith reduction were selected as the test group. 31 cases of posterior canal stones and 15 cases of horizontal semicircular canal stones, 29 cases of right ear and 17 cases of left ear. Fifty cases of healthy young volunteers were in the control group. Using the virtual reality SVV examination system, 0° SVV in the positive head were tested in the test group patients before and after the reduction of SVV , and were tested in the control group .The deviation angle of the SVV before and after the otolith reduction in the test group were analyzed. Results:Before otoliths reduction, the SVV was ï¼0.08±3.83ï¼° of right BPPV and was ï¼-1.69±2.23ï¼° of left BPPV. After otoliths reduction, the SVV was ï¼-1.52±3.74ï¼° of right BPPV and was ï¼-1.04±2.50ï¼° of left BPPV. In the control group, the SVV wasï¼-1.57±2.28ï¼° . The changes of SVV deflection angle between the control group and the right BPPV before the otolith reduction, and before and after the otolith reduction in the right BPPV were analyzed, and the differences were all statistically significant. There was no significant difference in SVV deflection angle between the left BPPVï¼before and after reductionï¼ and the control group. In the test group, after the otolith reduction, 18 cases had larger bias angles, 28 cases had smaller bias angle among which 13 cases the deviation angle even turned to the contralateral side. Conclusion:Utriculare dysfunction in patients with BPPV leads to the judgment error of SVV. Reduction of otolithoid can cause new stimulation to the eutricule and affect its functional status. SVV detection can provide help for the evaluation of utricular function in patients with BPPV.
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Membrana dos Otólitos , Canais Semicirculares , Humanos , Membrana dos Otólitos/fisiologia , FaceRESUMO
Corona Virus Disease 2019 (COVID-19), the novel coronavirus disease, is now a global pandemic. Vaccination can significantly reduce the mortality rate caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). There are currently several effective vaccines that have been introduced. Inactivated COVID-19 vaccine is one of these options and is generally considered safe. Neurofascin (NF) plays an important role in keeping the functionality of the node of Ranvier. We report here a rare case of anti-NF186+ chronic inflammatory demyelinating polyneuropathy (CIDP) in a 23-year-old male patient who was vaccinated with inactivated COVID-19 vaccine prior to the onset. This report adds a new possible rare side effect of a COVID-19 vaccine and provides a case for the clinical effectiveness of rituximab (RTX) in patients with anti-NF186+ CIDP.
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BACKGROUND: Asymptomatic transmission is a major concern for SARS-CoV-2 community spread; however, little information is available on demographic, virological characteristics and prognosis of asymptomatic cases. METHODS: All COVID-19 patients hospitalized in Guangdong Province from September 1, 2020 to February 28, 2021, were included and were divided into asymptomatic and symptomaticgroup. The source country of all patients, clinical laboratory test results, the genotype of virus and the time of SARS-CoV-2 RNA turning negative or hospitalization were confirmed. RESULTS: Total 233 patients from 57 different countries or regions were included, with 83 (35.6%) asymptomatic and 150 (64.4%) symptomatic patients. Asymptomatic cases were younger (P = 0.019), lower rate in comorbidities (P = 0.021) such as hypertension (P = 0.083) and chronic liver disease (P = 0.045), lower PCT (P = 0.021), DDI (P < 0.001) and ALT (P = 0.029), but higher WBC count (P = 0.002) and lymphocyte (P = 0.011) than symptomatic patients. As for SARS-CoV-2 subtypes, patients infected with B.1.1 (53.8%), B.1.351 (81.8%) and B.1.524 (60%) are mainly asymptomatic, while infected with B, B.1, B.1.1.63, B.1.1.7, B.1.36, B.1.36.1, B.1.36.16, B.1.5 and B.6 were inclined to be symptomatic. Patients infected with variant B.1.351 and B.1.524 spent longer time in SARS-CoV-2 RNA turn negative (26 days, P = 0.085; 41 days, P = 0.007) and hospitalization (28 days, P = 0.085; 43 days, P = 0.004). CONCLUSIONS: The asymptomatic cases are prone to develop in patients with younger age, less comorbidities andinfected with B.1.1 and B.1.524 variants. More attention should be paid for lineage B.1.524 because it can significantly prolong the SARS-CoV-2 RNA negative conversion time and hospitalization in infected cases.